**6. Solutions: do we have any?**

There is an urgent need to strategize to save the existing antimicrobials. We can perform that by following means to improve the existing ones, discover novel antibiotics, dig up the old socalled toxic compounds, scale up antibiotic stewardship, use inter-sectorial multidisciplinary approaches, educate the public and clinician's alike and reduce the antibiotics in livestock and agriculture to name a few [12].

#### **6.1. New targets/approaches**

Soil and marine environments appear to be rich ecological niches to discover new agents and so do the plants and animals. Co-trimoxazole was a perfect example of targeting two enzymes in a metabolic pathway producing synergism. Compounds can be synthesised artificially to target more than one mechanism. There is important role of whole genome sequencing and metagenomics to find the new targets.

We hope that novel hitherto unknown mechanisms of antibiotic resistance will be revealed which can be exploited to find new targets. The drugs targeting anti-virulence mechanisms are an attractive strategy and have shown some promising results. Other interesting approach may be to target/alter untapped metabolic pathways like fatty acid synthesis, proton motive force, quorum sensing, signal transduction, efflux pumps, etc. [12]. Many of such compounds are currently in experimental stages.

#### **6.2. Repurposing of compounds**

Some of the compounds are already approved by FDA for treatment of metabolic disorders and cancers also have antimicrobial properties and can be repurposed, e.g., the compound BPH-652 that inhibits squalene synthase involved in cholesterol biosynthesis and also inhibits dehydrosqualene synthase involved in virulence in *Staphylococcus aureus*, hence a good candidate for Methicillin-resistant *Staphylococcus aureus* (MRSA) [12].

#### **6.3. Considering conventional drugs**

The drugs used in the past, which have been revived and now are used to treat the infections caused by Gram-negative bacteria, include colistin, fosfomycin, temocillin and rifampicin [17].

#### **6.4. Combination therapy**

Finding a suitable antimicrobial treatment option for some of the highly drug-resistant bacteria can be really daunting, and many times, clinicians resort to using combinations without data pertaining to their efficacy. The main drugs in these combinations are polymyxins and tigecycline; however, additional drugs comprise carbapenems, tigecycline, fosfomycin, aminoglycosides, and rifampicin [17] where data on randomised control trials of these drugs is also lacking. The factors which need to be taken into account before an appropriate combination is used includes the targeted organism and its susceptibility profile, co-morbidities present in the patient and the site of the infection. More studies including pharmacokinetic and pharmacodynamics studies are required to find the ideal combinations [40].

#### **6.5. Phage therapy**

**6. Solutions: do we have any?**

6 Antimicrobial Resistance - A Global Threat

agriculture to name a few [12].

**6.1. New targets/approaches**

metagenomics to find the new targets.

There is an urgent need to strategize to save the existing antimicrobials. We can perform that by following means to improve the existing ones, discover novel antibiotics, dig up the old socalled toxic compounds, scale up antibiotic stewardship, use inter-sectorial multidisciplinary approaches, educate the public and clinician's alike and reduce the antibiotics in livestock and

**Figure 2.** Urgent, concerning and serious threats with respect to development of antimicrobial resistance.

Soil and marine environments appear to be rich ecological niches to discover new agents and so do the plants and animals. Co-trimoxazole was a perfect example of targeting two enzymes in a metabolic pathway producing synergism. Compounds can be synthesised artificially to target more than one mechanism. There is important role of whole genome sequencing and Phages have the advantage of high specificity for their hosts without any notable adverse effects. They were historically in use in Europe for treatment of bacterial infections such as skin/wound infections, urinary tract infections, ear infections and even osteomyelitis [41]. New interest has been generated in phage therapy, and it may turn out to be a useful adjunct to antibiotics. Coupling antibiotics with phages or inhibitors of enzymes appears to be an attractive strategy which may succeed in many cases [41].
